Purinergic receptors in renal autoregulation of normal and hypertensive rats

Abstract

Evidence points to ATr and its metabolite adenosine as being key regulators of renal vascular tone. THree separate families of receptors are predominately I . activated by ATP met~bolites; P2X, P2Y, and P1 purinergic receptors. Activation r of the ATP sensitive P2X1 receptor and the adenosine sensitive A1 receptor have both been implicated Js mediators of renal autoregulatory behavior. The first major aim of these sturdies tested the hypothesis that inhibition of the P2X1 receptor impairs whole kidney autoregulation of renal blood flow in vivo. During I acute inhibition of P2XI1 receptors, rats had significantly impaired autoregulatory behavior. However, during inhibition of adenosine-activated A1 receptors autoregulatory behavirr remained intact. These results highlight a predominant. role for P2X1 over A1 receptors in the autoregulation of renal blood flow in vivo. The second major ail of these studies addressed the consequences of I . hypertension on renal autoregulation during inhibition of ADP-sensitive P2Y12 I receptors. Initial results demonstrated that Ang 11-mediated hypertension significantly impairs Ltoregulatory ability and stimulates renal structural injury. Blockade of the P2Y J2 receptor in Ang 11-treated rats normalized autoregulatory I I ability and renal strudtural injury. Additionally, the Ang 11-mediated increase in renal lymphocyte pr,valence was decreased by P2Y 12 receptor inhibition. Results in Ang 11-trered rats suggest that P2Y12 receptors activation may be a contributor to deere sed autoregulatory efficiency. In both normotensive and hypertensive models t~e purinergic receptors have a major impact on the regulation of renal he~odynamics and autoregulation, providing potential therapeutic targets for the prevention of renal failure